The senile amyloid plaques and congophilic angiopathic lesions found in abundance in brain of patients with Alzheimer's disease are abnormal extracellular structures. The biochemical composition of these structures has been extensively studied to better understand their possible role in the pathogenesis of this dementing disease. The mature amyloid plaque is a complex structure, consisting of a central core of amyloid fibrils surrounded by dystrophic neurites, axonal terminals and dendrites, microglia and fibrous astrocytes. The amyloid core of the senile amyloid plaque, and which surrounds blood vessels to produce the congophilic angiopathy, is a peptide of 39 to 43 amino acids termed the .beta.-Amyloid (.beta.A) peptide, the A.beta. peptide, the A4 protein, or the .beta.A4 peptide. .beta.A peptide is found in the brain in Alzheimer's disease, Down's syndrome, hereditary cerebral hemorrhage of the Dutch type, and in old age. See, e.g., K. Kosik Science256, 780-783 (1992).
E. Kline et al., PCT Appln WO 91/16819 describes a method of treating Alzheimer's disease by administering the .beta.-amyloid peptide itself, or an active fragment thereof. H. Potter, PCT Appln WO 92/03474, describes a therapeutic method of treating individuals, such as Alzheimer's disease patients, to prevent the formation of an .alpha.-antichymotrypsin-.beta.-amyloid peptide complex by administering to the subject a synthetic peptide comprising a fragment of the .beta.-amyloid peptide.
The .beta.A peptide is produced by the abnormal proteolytic processing of a larger protein, the amyloid precursor protein (APP). APP itself has been identified in the senile amyloid plaque, and additional proteins which have been localized to senile amyloid plaques and angiopathic lesions include apolipoprotein E, alpha-1-antichymotrypsin, complement factors C1q and C3q, APP, and IgG. See, e.g., W. Strittmatter et al., Proc. Natl. Acad. Sci. 90, 1977 (1993); Abraham et al., Cell, 52, 487 (1988), Eikelenboom et al., Acta Neuropathol., 57, 239 (1982); McGeer et al., Canad. J. Neuro. Sci., 16, 516 (1989), Beyreuther et al., Brain Pathol., 1, 241 (1991); Ishii et al., Acta Neuropathol., 36, 243 (1976). The mechanisms by which these proteins aggregate in the extracellular space to associate with the senile amyloid plaque and congophilic angiopathic lesion are not known. Hence, there is an ongoing need for new ways to investigate and combat this disorder.